Hypothesis: We hypothesized that hypertension (HTN), of all known risk factors, is most closely linked to early WM tract injury in apparently healthy high risk relatives of patients with early-onset coronary artery disease (CAD).

Methods: DTI was acquired on a Phillips 3T MRI scanner (slice thickness 2.2 mm, field of view 212X212 mm and b-value 700 mm2/s) for relatives of CAD patients. The brain was segmented into 181 regions using the Eve Atlas, Large Deformation Diffeomorphic Metric Mapping paradigm, and 48 regions representing the deep WM were selected for analysis. Mean regional FA (rFA) was assessed using t-tests in persons with and without smoking, HTN, diabetes. Continuous variable association with rFA was tested using Spearman correlations. Covariate-adjusted GEE linear regression (corrected for nonindependence of families) was performed for regions meeting the Bonferroni threshold of 0.001 (0.05/48).

Conclusions: Of all of the risk factors, as hypothesized, HTN and SBP were significantly associated with early WM tract injury in areas related to cognition in middle-aged persons at risk for vascular disease.